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LABORATORY!MANUAL!!

SCH!3434!!ORGANIC!SYNTHESIS!

DEPARTMENT OF CHEMISTRY

KULLIYYAH OF SCIENCE IIUM!

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CONTENTS PAGE General Guidelines for Laboratory Safety Rules

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Components of Experimental Report

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EXPERIMENT 1 : The Aldol Condensation Reaction: Preparation of Benzalacetophenone (Chalcones)

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EXPERIMENT 2 : Multistep Reaction Sequence: The Conversion of Benzaldehyde of Benzilic Acid

9

EXPERIMENT 3 : Phase-Transfer Catalysis: Addition of Dichlorocarbene to Cyclohexene

17

EXPERIMENT 4 : Regioselective and Chemoselective Reduction of α,β-Unsaturated Carbonyl Compounds by NaBH4/Ba(OAc)2 as Reducing System

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General Guidelines for Laboratory Safety Rules

Please follow the following guidelines for your safety in the laboratory:

1. Every time you enter the lab, do not forget to wear goggles Students are advised not to wear contact lens in the lab as the solvents (particularly organic solvents) are mostly volatile and flammable.

2. Dress properly during a laboratory activity. Shoes must completely cover the foot. No sandals allowed in the laboratory.

!3. Do not bring food and drink into the laboratory.

4. Be prepared for your work in the laboratory. Read all procedures thoroughly before entering the laboratory. Never fool around in the laboratory. Horseplay, practical jokes, and pranks are dangerous and prohibited.

5. Observe good housekeeping practices. Work areas should be kept clean and tidy at all times

6. All chemicals in the laboratory are to be considered dangerous. Avoid handling chemicals with fingers. Always use a tweezer.

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Components of Experimental Report

For each experiment done, a student is required to write a report and submit to the respective lecturer. In your report, please include the following components:

a) Title and date - What is the title of the experiment given and date of experiment was conducted.

b) Introduction % In the introduction, the student needs to write what is the aims/objectives

of the experiment, what are the instruments used and the balanced chemical equations involved in the experiment.

c) Procedure of the experiment % It is better to write in your own words (flow chart, mind map) as it will

reveal your understanding of the experiment carried out.

d) Data and Observations % The observations are described as the progress in the experiment. It

includes (but not limited to) colour and temperature changes, appearance of precipitate, the weight of reagent and products, etc.

e) Discussion of data and conclusion % In this section, you are required to interpret the data obtained and

supported by appropriate references.

f) References % The references should be taken from books, journals and website.

g) Questions - Answer all the questions in the lab manual when applicable.

Laboratory(Grading(Rubric(

Component 0 1-2 3-4 5 Marks (30)

1 Introduction

No real introduction. Weak or missing primary elements.

Either lacks clarity or is missing one of the primary elements.

Presents a clear summary of the aims of the study and its significance. Briefly describes experimental design. Probably includes one or more references to supporting sources.

/5

2 Materials & methods

Methods barely mentioned.

Some methods are omitted; others are presented in a piecemeal, vague form.

Some methods are presented so briefly and/or vaguely that it is unclear how or why they were done. May be some written as a protocol rather than a description.

Gives a clear picture of the methods and materials used. Does not use prescriptive language. Uses specific, not general, terminology. Detailed, step-by-step procedures are clearly referenced. Avoids long, redundant descriptions.

/5

3

Result

No logical connection between methods and data. Irrelevant data may be included, and relevant data left out. No legends.

Data is presented haphazardly. It is sometimes not possible to tell what material or procedure was used to obtain the data.

Some data may be missing, or legends may be brief, vague or uninformative.

All figures and tables have titles and legends. All results are clearly presented, with a logical sequence. Controls are clearly indicated.

/5

4

Discussion & Conclusion

Mostly a restatement of results. No analysis given. No recognition of error sources. No

Very little analysis of the results. Statements are vague and general. Inconsistencies are explained by 'human

There may be some lack of clarity. Did the writer understand why certain methods were used, and how

It is clear that the methods and results have been understood. The results (including controls) are related to the questions posed and analyzed for their

/5

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understanding of controls. No conclusion

error' or something similar. Conclusion shows little effort and reflection

the results could shed light on the questions asked? Incomplete analysis of inconsistencies and unexpected results. Conclusion includes a general overview of the experiment and what was learned from the experiment

effectiveness. Possible explanations for inconsistencies and/or unexpected results are given. Conclusion includes a summary of the experiment, whether the findings supported the hypothesis, possible sources of error, and what was learned from the experiment

5 Questions

Questions not answered

Questions answered but with a lack explanation

Questions answered but with little explanation

Questions answered and showed a good understanding on the relevant topic with a good support of full explanation

/5

6

Writing Quality (including references)

Frequent grammatical errors: incomplete sentences, tense changes, misspellings. No reference at all.

Apparently not proofread for errors. Reference not following the format.

An occasional error Reference with occasional error in format

No spelling or grammatical errors. Able to cite and write complete reference using IIUM format

/5

30

(

EXPERIMENT 1 The Aldol Condensation Reaction: Preparation of Benzalacetophenone (Chalcones) Apparatus: 50-mL Erlenmeyer flask spatula beaker (50 mL) BÜchner funnel (& flask) Chemicals: 3-nitrobenzaldehyde Acetophenone 95% ethanol sodium hydroxide Benzaldehyde reacts with a ketone in the presence of base to give α,β-unsaturated ketones. This reaction is an example of a crossed aldol condensation where the intermediate dehydrates to produce the resonance-stabilised unsaturated ketone.

Cross aldol condensations of this type proceed in high yield since benzaldehyde cannot react with itself by an aldol condensation reaction because it has no α-hydrogen. Likewise, ketones do not react easily with benzaldehyde. In this experiment, procedures are given for the preparation of benzalacetophenones (chalcones). You should choose one of the substituted benzaldehydes and react it with the ketone, acetophenone. Procedure Place 0.75 g (5 mmol) of 3-nitrobenzaldehyde (MW = 151.1) into a 50-mL Erlenmeyer flask. Add 0.60 mL of acetophenone (MW = 120.2, d = 1.03 g/mL) and 4.0 mL of 95% ethanol to the flask containing the aldehyde. Swirl the flask to mix the reagents and dissolve any solids present. It may be necessary to warm the mixture on a steam bath or hot plate to dissolve the solid. If this is necessary, then the solution should be cooled to room temperature before proceeding with the next step. Add 0.5 mL of sodium hydroxide solution (note to instructor: reagent prepared by dissolving 6.0 g NaOH into 10 mL of water). Swirl the mixture until it solidifies or until the entire mixture becomes very cloudy. Isolation of the crude product. Add 10 mL of ice water to the flask. If a solid is present at this point, stir the mixture with a spatula to break up the solid mass. If an oil is present, stir the mixture until the oil solidifies. Transfer the mixture to a beaker with

C6H5 CH

O+ H3C C R

OHO- C6H5 C

H

OH

CH2 C

O

R

Intermediate

H2O H

C6H5 H

CO

R

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15 mL of ice water. Stir the precipitate to break it up and then collect the solid in a BÜchner funnel. Wash the product with cold water. Allow the solid to air dry for about 30 minutes. Weigh the solid and determine the percentage yield. Crystallisation of the Benzalacetophenone (Chalcone). Crystallise all of the sample from hot 95% ethanol. Use about 4 mL of ethanol per gram of solid. Scratch the flask to induce crystallisation while cooling. Determine the melting point of your product. Obtain the proton and carbon-13 NMR spectrum. Questions:

1. Give the mechanism for the preparation of the benzalacetophenone using the given aldehyde in the experiment.

2. Draw the structure of the cis and trans isomers of the compound that you prepared. Why did you obtain the trans isomer?

3. Using proton NMR, how could you experimentally determine that you have the trans isomer rather than the cis isomer?

4. Provide the starting materials needed to prepare the following compounds:

H3CH2CHC C

CH3

C

O

H C C

H

C

O

PhPh

H3C

H3CO CH

CH COCH

CH OCH3

a) b)

c)

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EXPERIMENT 2 Multistep Reaction Sequence: The Conversion of Benzaldehyde of Benzilic Acid Apparatus: 50-mL Erlenmeyer flask BÜchner funnel (vacuum filtration) magnetic stirring bar condenser (reflux) – joint that can fit the flask stirring hot plate 25-mL round-bottom flask heating mantle 100-mL Erlenmeyer flask filter paper pH paper 50 or 100 mL- measuring cylinder stopcock grease Chemicals: Thiamine hydrochloride 95% ethanol NaOH Benzaldehyde Boiling stone KOH concentrated hydrochloric acid concentrated nitric acid The Experiment demonstrates multistep synthesis of benzilic acid starting from benzaldehyde. First, benzaldehyde is converted to benzoin using a thiamine-catalysed reaction. This part of the experiment demonstrates how a ‘green’ reagent can be utilised in organic chemistry. Then, nitric acid oxidises benzoin to benzil. Finally, benzil is rearranged to benzilic acid. A. Preparation of Benzoin by Thiamine Catalysis In this experiment, two molecules of benzaldehyde will be converted to benzoin condensation reaction:

Thiamine hydrochloride is structurally similar to thiamine pyrophosphate (TPP), which is a coenzyme universally present in all living systems. It catalyses several biochemical reactions in natural systems.

H

O2

Thiaminehydrochloride O

OH

BenzoinBenzaldehyde

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Thiamine binds to an enzyme before the enzyme is activated. The enzyme also binds to the substrate (protein). Without the coenzyme thiamine, no chemical reaction would occur.The coenzyme is the chemical reagent.The protein molecule (enzyme) helps and mediates the reaction by controlling stereochemica;, energetic and entropic factors, but it is nonessential to the overall course of the reactions that it catalyses. The most important part of the entire thiamine molecule is the central ring, the thiazole ring, which contains nitrogen and sulphur. This ring constitutes the ragent portion of the coenzyme. Experiments with the model compound 3,4-dimethylthiazolium bromide found that it rapidly exchanged the C-2 proton for deuterium in D2O solution. At a pD of 7 (no pH here), this proton was completely exchanged in seconds! This indicates that the C-2 proton is more acidic than expected. It is apparently easily removed because the conjugate base is a highly stabilised ylide. An ylide is a compound or intermediate with positive and negative formal charges on adjacent atoms.

The sulphur atom plays an important role in stabilising this ylide. This was shown by comparing the rate of exchange of 1,3-dimethyl-imidazolium ion with the rate for the thiazolium compound shown in the previous equation. The dinitrogen compound exchanged its C-2 proton more slowly than the sulfur-containing ion. Sulfur, being in the third row of the periodic chart has d orbitals available for bonding to adjacent atoms. Thus is has fewer geometrical restrictions than carbon and nitrogen atoms do and can form carbon-sulfur multiple bonds in situations in which carbon and nitrogen normally would not. In this experiment, we will utilise thiamine hydrochloride to catalyse the benzoin condensation. The mechanism (only thiazole ring is shown) is shown below:

N

N

H3C

NH2

N

SH

CH3

OPOH

OO P

O

OHO-

TPP

N

N

H3C

NH2

N

SH

CH3

OH

Cl-

thiazole ring

Thiamine hydrochloride

N S

H

H3C

H3CBr-

C-2

D2O28 oC N S

H3C

H3C N S

D

H3C

H3CBr-

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Procedure Add 1.5 g thiamine hydrochloride to a 50-mL Erlenmeyer flask. Dissolve the solid in 2 mL of water by swirling the flask. Add 15 mL of 95% ethanol and swirl the solution until it is homogeneous. To this solution, add 4.5 mL of an aqueous sodium hydroxide (instructor: dissolve 40 g of NaOH in 500 mL water) solution and swirl the flask until the bright yellow colour fades to a pale yellow colour. Carefully measure 4.5 mL of pure benzaldehyde and add it to the flask. Swirl the contents of the flask until they are homogeneous. Stopper the flask and allow it to stand in a dark place for at least two days. Isolation of Crude Benzoin. If crystals have not formed after two days, initiate crystallisation by scratching the inside of the flask with a glass stirring rod. Allow about 5 minutes for the crystals of benzoin to fully form. Place the flask, with crystals into an ice bath for 5-10 minutes. If for some reason the product separates as an oil, it may be helpful to scratch the flask with a glass rod or seed the mixture by allowing a small amount of solution to dry on the end of a glass rod and then placing this into the mixture. Cool the mixture in an ice bath before filtering. Break up the crystalline mass with a spatula, swirl the flask rapidly and quickly transfer the benzoin to a BÜchner funnel under vacuum. Wash the crystals with two 5-mL portions of ice-cold water. Allow the benzoin to dry in the BÜchner funnel by drawing air through the crystals for about 5 minutes. Transfer the benzoin to a watch glass and leave it in an oven set at about 100 oC for a few minutes to dry. Weigh the benzoin and calculate the percentage yield based on the amount of benzaldehyde used initially. Determine the melting point. Purify the crude benzoin by crystallisation from hot 95% ethanol using Erlenmeyer flask. After the crystals have cooled in an ice bath, collect the crystals on a BÜchner funnel. The product may be dried in a few minutes in an oven set at about 100 oC. Determine the melting point of the purified benzoin.

SN R

CH3R

HB-

SN R

CH3R

H

PhOH B

SN R

CH3R

OHHPh

B- SN R

CH3R

PhOHH

PhOH B

SN R

CH3R

OHPhH

OHPh

SN R

CH3R

OPhH

OHPh B-H

SN R

CH3R+

Ph O

HPhOH

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Questions:

1. The infrared spectra of benzoin and benzaldehyde are given. Interpret the principal peaks in the spectra.

2. Draw a mechanism for the cyanide-catalysed conversion of benzaldehyde to

benzoin, The intermediate (shown in brackets), is thought to be involved in the mechanism.

B. Preparation of Benzil In this experiment, benzil is prepared by oxidation of an α-hydroxyketone, benzoin prepared earlier. This oxidation can be done with mild oxidising agents such as Fehling’s solution or copper sulphate in pyridine. In this experiment, it is performed with nitric acid.

2 CHO CN- C CHO OH

COH

CN

OH

O

O

OHNO3

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Place 2.5 g of benzoin into a 25-mL round-bottom flask and add 12 mL of concentrated nitric acid. Add a magnetic stirring bar and attach a water condenser.In a hood, set up the apparatus for heating in a hot water bath. Heat the mixture in a hot water bath at about 70 oC for 1 hour, with stirring. Avoid heating the mixture above this temperature to reduce the possibility of forming a by-product. During the 1-hour heating period, nitrogen oxide gases will be evolved. If it appears that gases are still being evolved after 1 hour, continue heating for another 15 minutes but then discontinue heating at that time. Isolation of Crude Benzil. Pour the reaction mixture into 40 mL of cool water and stir the mixture vigorously until the oil crystallises completely as a yellow solid. Scratching or seeding will be necessary to induce crystallisation. Vacuum filter the crude benzyl on a BÜchner funnel and wash it well with cold water to remove the nitric acid. Allow the solid to dry thoroughly by drawing air through the fiter. Weigh the crude benzyl and calculate the percentage yield of the crude benzil. Crystallisation of product. Purify the solid by dissolving it in hot 95% ethanol in an Erlenmeyer flask using a hot plate as the heating source. Be careful not to melt the solid on the hot plate. You can avoid melting the benzil by occasionally lifting the flask from the hot plate and swirling the contents of the flask. You want the solid to dissolve in the hot solvent rather than melt. You will obtain better crystals if you add a little extra solvent after it dissolves completely. Remove the flask from the hot plate and allow the solution to cool slowly. As the solution cools, seed it with a solid product that forms on a spatula after the spatula is dipped into the solution. The solution may become supersaturated unless this done and crystallisation will occur too rapidlt. Yellow crystals are formed. Cool the mixture in an ice bath to complete the crystallisation. Collect the product on a BÜchner funnel. Continue drawing air through the crystals on the BÜchner funnel by suction for about 5 minutes. Then remove the crystals and air-dry them. Yield Calculation and Melting-Point Determination. Weigh the dry and calculate the percentage yield. Determine the melting point. Obtain the infrared spectrum of benzil. Compare the spectrum with benzoin and note the differences.

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C. Preparation of Benzilic Acid In this experiment, benzilic acid will be prepared by causing the rearrangement of the α-diketone benzil.

Add 2.00 g benzil and 6 mL 95% ethanol to a 25-mL round-bottom flask. Place a boiling stone in the flask and attach a reflux condenser. Be sure to use a thin film of stopcock grease when attaching the reflux condenser to the flask. Heat the mixture with a heating mantle or hot plate until the benzil has dissolved. Using a Pasteur pipette, add dropwise 5 mL of an aqueous potassium hydroxide solution downward through the reflux condenser into the flask. Gently boil the mixture with occasional swirling of the contents of the flask. Heat the mixture at reflux for 15 minutes. The mixture will be blue black in colour. As the reaction proceeds, the colour will turn to brown, and the solid should dissolve completely. Solid potassium benzilate may form during the reaction period. At the end of the heating period, remove the assembly from the heating device and allow it to cool for a few minutes. Crystallisation of Potassium Benzilate. Detach the reflux condenser when the apparatus is cool enough to handle. Transfer the reaction mixture, which may contain some solid, with a Pasteur pipette into a small beaker. Allow the mixture to cool to room temperature and then cool in an ice-water bath for about 15 minutes until crystallisation is complete. It may be necessary to scratch the inside of the beaker with a glass stirring rod to induce crystallisation. Crystallisation is complete when virtually the entire mixture has solidified. Collect the crystals on a BÜchner funnel by vacuum filtration and wash the crystals thoroughly with there 4-mL portions of ice-cold 95% ethanol. The solvent should remove most of the colour from the crystals. Transfer the solid, which is mainly potassium benzilate, to a 100-mL Erlenmeyer flask containing 60 mL of hot (70 oC) water. Stir the mixture until all solid has dissolved or until or appears that the remaining solid will not dissolve. Any remaining solid will likely form a fine suspension. If solid does remain in the flask, gravity-filter the hot solution through fast-fluted filter paper until the filtrate is clear. If no solid remains in the flask, the gravity filtration step may be omitted. In either case, proceed to the next step. Formation of Benzilic Acid. With swirling of the flask, slowly add dropwise 1.3 mL of concentrated hydrochloric acid to the warm solution of potassium benzilate. As the solution becomes acidic, solid benzilic acid will begin to precipitate. Keep adding the

Ph C C Ph

O OKOH

Ph C C OH

O O K+

Ph

Ph C C OH

O OK+

Ph

Ph C C O

OH OK+

Ph

H3O+Ph C C OH

OH O

Ph

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hydrochloric acid until the solid stays permanently and then start monitoring the pH. The ideal pH should be about 2; if it is higher than this, add more acid and check the pH again. Allow the mixture to cool to room temperature and then complete the cooling in an ice bath. Collect the benzilic acid by vacuum filtration using a BÜchner funnel. Wash the crystals with two 30-mL portions of ice-cold water to remove potassium chloride slat that sometimes coprecipitates with benzilic acid during the neutralisation with hydrochloric acid. Remove the wash water by drawing air through the filter. Dry the product thoroughly by allowing it to stand until the next laboratory period. Melting point and Crystallisation of Benzilic Acid. Weigh the dry benzilic acid and determine the percentage yield. Determine the melting point of the dry product. Recrystallise the product using hot water if necessary. Questions:

1. Show how to prepare the following compounds starting from the appropriate aldehyde.

2. Give the mechanisms for the following transformations:

H3CO C

OH

CO2H

OCH3

a) b)O

COHCO2H

O Oa)

1) KOH

2) H+

HO CO2H

b)

Ph C C Ph

O O-OCH3

CH3OHPh C C OCH3

OH O

Ph

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3. Interpret the infrared spectrum of benzilic acid.

Tran

mitt

ance

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EXPERIMENT 3 Phase-Transfer Catalysis: Addition of Dichlorocarbene to Cyclohexene Apparatus: 25-mL round-bottom flask 250-mL beaker hot plate stirrer magnetic stir bar glass stopper reflux apparatus (condenser that can fit the round-bottom flask joint) 125-mL separatory funnel methylene chloride Erlenmeyer flask (small & medium) Pasteur pipette Steam bath Chemicals: Cyclohexene NaOH Chloroform benzyltriethylammonium chloride anhydrous sodium sulphate NaCl A haloform, CHX3 will react with a strong base to give a highly reactive carbine species CX2 by reactions (1) and (2). In the presence of an alkene, this carbine adds to the double bond to produce a cyclopropane ring (3).

Normally, the reaction has been carried out in one homogeneous phase in anhydrous t-butyl alcohol solvent, using t-butoxide ion as the base [t-Bu = C(CH3)3].

XCX

X H + O HXCX

X + H2O (1)

X

C

X

Xslow

CH2

X

X + X- (2)

CH2

X

X + C CC

C

C

X X

(3)

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Unfortunately, this technique requires time and effort to give good results. In addition, water must be avoided to prevent conversionof the haloformand carbine to formate ion and carbon monoxide by the undesirable base-catalysed reactions. As an alternative to homogeneous reaction, a two-phase reaction can be considered when the organic phase contains the alkene and a haloform CHX3 and the aqueous phase contains the base –OH. Unfortunately, under these conditions the reaction will be very slow, because the two primary reactants CHX3 and –OH are in different phases. The reaction rate can be substantially increased, however, by adding a quarternary ammonium salt such as benzyltriethylammonium chloride as a phase-transfer catalyst.

Other common catalysts are tetrabutylammonium bisulfate, trioctylmethylammonium chloride and cetyltrimethylammonium chloride. All these catalysts have at least 13 carbon atoms. The numerous carbon atoms give the catalyst organic character (hydrophobic) and allow it to be soluble in the organic phase. At the same time, the catalyst also has ionic character (hydrophilic) and can therefore be soluble in the aqueous phase. Because of this dual nature, the large cation can cross the phase boundary efficiently and transport a hydroxide ion from the aqueous phase to the organic phase. Once in the organic phase, the hydroxide ion will react with the haloform to give dihalocarbene by reactions 1 and 2. Water, a product of the reaction, will move from the organic phase to the aqueous phase, thus keeping the water concentration in the organic phase section on quaternary ammonium salt catalysis.

HCX3 + Ot Bu + C C C

C

C

X X

+ HOt Bu + X-t-Bu-OH

CH2 N

CH2CH3

CH2CH3

CH2CH3 Cl-

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Crown ethers are very expensive to ammonium salts and are not used as widely for large-scale reactions. In some cases, however, these ethers may be necessary to obtain an efficient and high-yield reaction. In this experiment, you will prepare 7,7-dichlorobicyclo[4.1.0]heptane (also known as 7,7-dichloronorcarane) by the reaction

Chloroform and base are used in excess in this reaction. Although most of the chloroform reacts to give the 7,7-dichloronorcarane via carbine intermediate, a significant portion is hydrolysed by the base to formate ion and carbon monoxide. Bromoform, CHBr3, can be used to prepare the corresponding 7,7-dibromonorcarane via the dibromocarbene. Procedure Pre-weigh a 25-mL round-bottom flask with glass stopper and transfer 2.0 mL of cyclohexene to the flask in a hood. Stopper the flask and re-weigh it to determine the weight of cyclohexene. Add 5.0 mL of 50% aqueous sodium hydroxide (instructor: Dissolve 50 g of NaOH in 50 mL of water. Cool the solution to RT) to the flask, being careful to avoid getting any solution on the glass joint. In a hood, add 5.0 mL of chloroform to the round-bottom flask. Weigh 0.20 g of the phase-transfer catalyst, benzyltriethylammonium chloride, on a smooth piece of paper and reclose the bottle immediately (it is hygroscopic!). Add the catalyst to the flask and stopper it. In a hood, prepare a hot water bath at 40 oC using a 250-mL beaker and hot plate. Assemble a reflux apparatus and clamp the condenser so that the flask is immersed in the water bath. Stir the mixture as rapidly as possible for 1 hour. An emulsion forms during this time.

C CCHX3 +Organic phase

C C

CHX3 +

Aqueous phase

C

C

C

X X+

HO- CX2 + H2O + R4N+

X-

H2O + NaOH

R4N+ X-

Phase boundary

+ CHCl3 + OH-Cl

Cl + H2O + Cl-

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Following this reaction time, remove the flask from the water bath and allow the reaction mixture to cool to room temperature. Pour the reaction mixture into a small beaker and remove the magnetic stir bar. Transfer the mixture to a 125-mL separatory funnel. Add 8 mL of water and 5 mL of methylene chloride to the mixture. Shake the mixture with venting for about 30 seconds and allow the layers to separate. Swirl the funnel gently to help break up the emulsion. Drain the lower methylene chloride layer into a small Erlenmeyer flask. The small amount of emulsion that forms at the interface should be left behind with the aqueous layer. Add another 5-mL portion or methylene chloride, shake the mixture for 30 seconds, and allow the layers to separate. It may be necessary to swirl the funnel gently or tap the funnel gently with your finger to help break up the emulsion. Combine the lower organic layer with the first extract. Discard the remaining aqueous layer into the container for aqueous waste, avoiding contact with the basic solution. Rinse the funnel with water and pour the combined organic layers back into the separatory funnel. Extract the mixture with 10 mL of saturated sodium chloride solution. Drain the lower methylene chloride layer, avoiding any emulsion that might be present at the interface, into a dry Erlenmeyer flask containing 0.5 g of anhydrous sodium sulphate. Stopper the flask and swirl it occasionally for at least 10 minutes to dry the organic layer. Using a dry Pasteur pipette, transfer about half of the dried organic layer to a dry, preweighed centrifuged tube. Evaporate the methylene chloride, together with any remaining cyclohexene and chloroform in a hood. Following removal of methylene chloride, you are left with 7,7-dichloronorcarane of sufficient purity for spectroscopy. Weigh the centrifuge tube, determine the weight of product and calculate the percentage yield. Obtain the infrared spectrum. Questions:

1. Why did you wash the organic phase with saturated sodium chloride solution? 2. What short chemical test could you make on the product to indicate whether

cyclohexene is present or absent? 3. Would you expect 7,7-dichloronorcarane to give a positive sodium-iodide-in-

acetone test? 4. Assign the C-H stretch for cyclopropane ring hydrogens in the infrared

spectrum. 5. Suggest why it may be necessary to use a large excess of chloroform in this

reaction. 6. A student obtained a proton NMR spectrum of the product isolate in this

experiment. The pectrum shows peaks at about 7.3 and 5.6 ppm.What do you think these peaks indicate? Are they part of 7,7-dichloronorcarane spectrum?

7. Draw the structures of the products that you would expect from the reactions of cis- and trans-2-butene with dichlorocarbene.

8. Draw the structures of the expected dichlorocarbene adduct of methyl methacrylate (methyl 2-methylpropenoate). With compounds of this type, another product could have been obtained. It is the chloroform adduct to the double bond (Michael-type reaction). What would this structure look like?

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EXPERIMENT 4 Regioselective and Chemoselective Reduction of α ,β-Unsaturated Carbonyl Compounds by NaBH4/Ba(OAc)2 as Reducing System Apparatus: 10-mL round-bottom flask Condenser (to fit the RB flask) Magnetic stirrer TLC paper plates Chemicals: Benzylideneacetone Barium acetate n-hexane Ethyl acetate dichloromethane anhydrous sodium sulphate Procedure In a 10-mL round-bottom flask equipped with a magnetic stirrer and a condenser, a solution of benzylideneacetone (0.146 g, 1 mmol) and Ba(OAc)2 (0.05 g, 0.2 mmol) in CH3CN (3 mL) was prepared, and NaBH4 (0.076 g, 2 mmol) was added. The resulting mixture was stirred under reflux conditions. TLC monitored the progress of the reaction (eluent; n-hexane/EtOAc: 9/1). After completion of the reaction within 15 minutes, distilled water (5 mL) was added to the reaction mixture and it was stirred for an additional 5 minutes. The mixture was extracted with CH2Cl2 (3 x 8 mL) and dried over anhydrous sodium sulphate. Evaporation of the solvent afforded the pure 4-phenyl-3-buten-2-ol. Questions:

1. Define and explain the terms ‘regioselective’ and ‘chemoselective’. 2. Reduction of α,β-unsaturated carbonyl compounds can follow two pathways:

addition to carbonyl group and addition to conjugated double bonds. a) Give the mechanism for each of the pathways b) How the selectivity of the reactions are controlled?

References

1. Any organic chemistry reference books 2. Mohamadi, M., Setamdideh, D. and Khezri, B., (2013), Organic Chemistry

International, 13, 1-5.